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WO1986000530A1 - Procede de preparation de gamma globuline adequate pour une administration intraveineuse - Google Patents

Procede de preparation de gamma globuline adequate pour une administration intraveineuse Download PDF

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Publication number
WO1986000530A1
WO1986000530A1 PCT/EP1985/000320 EP8500320W WO8600530A1 WO 1986000530 A1 WO1986000530 A1 WO 1986000530A1 EP 8500320 W EP8500320 W EP 8500320W WO 8600530 A1 WO8600530 A1 WO 8600530A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
polyethylene glycol
gamma globulin
buffer
concentration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP1985/000320
Other languages
English (en)
Inventor
Jürgen-Dietrich Friedrich FIECHTL
Bernhard Kerner
Jürgen Holzapfel
Martin Puschmann
Tokusuke Kimura
Fumio Kurosu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Woelm Pharma GmbH and Co
Original Assignee
Woelm Pharma GmbH and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26091956&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1986000530(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Woelm Pharma GmbH and Co filed Critical Woelm Pharma GmbH and Co
Priority to JP60503125A priority Critical patent/JPH0816065B2/ja
Priority to FI860350A priority patent/FI84136C/fi
Publication of WO1986000530A1 publication Critical patent/WO1986000530A1/fr
Priority to DK097286A priority patent/DK164023C/da
Priority to NO86860848A priority patent/NO168943C/no
Anticipated expiration legal-status Critical
Priority to JP7263622A priority patent/JPH08319241A/ja
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
    • C07K16/065—Purification, fragmentation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • This invention relates to a product containing gamma globulin suitable for intravenous administration and a process for producing the product.
  • USP 4,126,605 (Schneider) describes a process for ob ⁇ taining a product suitable for intravenous administration from Cohn Fraction II gamma globulin.
  • Cohn Fraction II is dissolved in a buffered aqueous solution at pH 6.7. The solution contains hydroxyethyl starch. After filtering the solution, polyethylene glycol is added to a concen ⁇ tration of 10%. After removal of the precipitate, additi ⁇ onal polyethylene glycol is added to the solution to a concentration of 20%. The precipitate which results is improved unmodified gamma globulin suitable for intra- venous use.
  • the gamma globulin useful as the starting material for the product and process of the current invention is well known in the art.
  • This gamma globulin preparation is dissolved in an aqueous solution at a neu ⁇ tral pH.
  • the aqueous solution has a low ionic strength.
  • the low ion concentration can be derived from salt present in the starting gamma globulin preparation or can be due to added buffer. All physiologically tolerated salts are suitable as buffers. These include phosphate, citrate and trihydroxy-ethyl-amino-methane.
  • the ionic concentration can be within the range of 0.001-0.015 mol/1. If buffer is added, it is preferred that the range be 0.01-0.015 mol/1.
  • the pH of the solution can be adjusted to 7.0 - 0.1 by addition of a suitable acid or base, for example, citric acid, sodium citrate or, if needed, sodium hy ⁇ droxide; citrate is preferred.
  • a suitable acid or base for example, citric acid, sodium citrate or, if needed, sodium hy ⁇ droxide; citrate is preferred.
  • the gamma globulin is dissolved in the solution in a concentration of 1-7% by weight.
  • the con ⁇ centrate is 3.1-4.9%.
  • hydrocolloid such as -hydroxyethyl starch, dextrose, albumin, polyalcohol and polyvinyl pyrrolidone as disclosed in USP 4,126,605.
  • the in ⁇ soluble impurities are removed from the solution by, for example, decantation, filtration, or centrifu- gation. (c) Adding polyethylene glycol to the separated solution.
  • PEG polyethylene glycol
  • the PEG will have a molecular weight average of 4000.
  • the PEG may be added to the supernatant in bulk, as a powder or as solution having PEG dissolved therein. PEG is added at room temperature to the separated solution to a concentration of 3-6% by weight, preferably 4.0-5.5% by weight.
  • the buffers useful are listed above.
  • the ionic concentration of the solution after the addition of buffer should be 0.025-0.25 mol/1.
  • the concentration of PEG in the solution is increased to 9-16% by weight by the addition of PEG.
  • the temperature of the solution at this step may be reduced to 0-10°C, however, it may remain at room temperature.
  • the purified immunoglobulin which precipitates after in ⁇ creasing the concentration of PEG is then separated by means of gentle separation procedures, for example, de- cantation, filtration, or centrifugation.
  • the separation is by means of centrifugation.
  • the obtained purified gamma globulin is native, has low ACA and is suitable for use in products for intravenous administration.
  • the purified gamma globulin is preferably dissolved in aqueous solution at a concentration 2-10%, preferably about 5%.
  • the solutions may also contain buffer, e.g., citrate and/or phosphate, sugar, e.g. glucose, maltose, sucrose, and an isotonicity agent, e-g- NaCl; citrate is preferred.
  • the average anti-complementary activity (ACA) of the pro ⁇ duct is approximately 10 CH 5Q u/ml or less (protein con- centrate of 5%) .
  • Cohn-Fraction-II-Powder is dissolved in a 0.01 molar phosphate-citrate-buffer (7.00 pH, 10°C) with careful stirring to a protein concentration of 3.5%. Hydroxyethyl starch is present in a concentration of .5%.
  • the precipitate formed is removed and the solution is clarified by layer filtrations in one filtration step.
  • the the protein concentration is adjusted to 2.5% and the phosphate-citrate concentration is adjusted to 0.12 molar and the pH is adjusted to 7.0 + 0.1 by addition of a 0.5 molar phosphate-citrate-buffer (molarity related to con ⁇ tent of phosphate/citrate) .
  • a 0.5 molar phosphate-citrate-buffer moolarity related to con ⁇ tent of phosphate/citrate
  • the supernatant is decantated from the precipitate formed and is clarified by layer filtration.
  • the clarified supernatant is cooled to a temperature of 10°C and then diluted, with stirring, with a 50% solution of PEG 4000 in a 0.03 molar phosphate-citrate-buffer at 10°C to a PEG 4000 concentration of 14%.
  • the precipitate formed (paste) is collected by continuous centrifugation.
  • the so-prepared solution shows the following characteristic values: protein: 5.4% pH 7.00 + 0.05 glucose: 2.5% +_ 0.5% osmolarity: 300 - 330 mosmol/1
  • the solution is sterile filtered and placed into vials and, optionally, lyophilized.
  • Cohn-Fraction-II-Powder is dissolved, at room temperature and pH of 7, in water for injection with careful stirring to a protein concentration of 5%. Hydroxyethyl starch is present in a concentration of .5%.
  • the precipitate formed is removed and the solution is clarified by layer filtration within one filtration step.
  • Polyethylene glycol (PEG 4000) as a 40% solution, is added, under careful stirring, to a concentration of 4.0%.
  • the precipitate is removed by depth filtration.
  • To the clear supernatant .3M phosphate buffer is added to a con ⁇ centration of 10% by volume and the PEG 4000 concentration is increased 10.4%.
  • the precipitate formed (paste) is collected by continous centrifugation.
  • the paste is dissolved in a lOmM citrate/lOmM phosphate buffer (pH 7.0 + 0.1) additionally containing 0.9% NaCl and2.5% glucose.
  • the redissolved solution had the following characteris ⁇ tics: protein: 5.4% pH 7.00 + 0.05 glucose: ' 2.5% +_ 0.5%
  • the solution is sterile filtered, filled into bottles, and, optionally freeze-dried.
  • the yield of immunoglobulin based on percentage of immuno ⁇ globulin in Cohn fraction II is excess of 70%.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Un procédé de préparation de gamma globuline adéquate pour une administration intraveineuse comporte la dissolution de gamma globuline précipitée à partir de sang ou de produits sanguins dans une solution, la séparation du précipité non dissous de la solution, l'addition de polyéthylène glycol à la solution séparée, la séparation du précipité de la solution de polyéthylène glycol, l'accroissement de la concentration du polyéthylène glycol dans la solution, la séparation de gamma globuline purifiée précipitée de la solution de polyéthylène glycol à concentration supérieure, la dissolution de la gamma globuline purifiée dans une solution adéquate pour une administration intraveineuse, ce procédé étant amélioré par la dissolution de la gamma globuline précipitée à partir de sang dans une solution à pH neutre, l'addition de polyéthylène glycol à la première étape à une concentration de 4,0-5,5% en poids et l'accroissement de la concentration du polyéthylène glycol dans la deuxième étape à au moins 9% mais pas moins de 16% en poids, ainsi que l'addition d'un tampon à la solution juste avant l'addition du polyéthylène glycol dans l'une des deux étapes d'addition de polyéthylène glycol.
PCT/EP1985/000320 1984-07-07 1985-07-03 Procede de preparation de gamma globuline adequate pour une administration intraveineuse Ceased WO1986000530A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP60503125A JPH0816065B2 (ja) 1984-07-07 1985-07-03 静脈注射用のガンマグロブリンの製法
FI860350A FI84136C (fi) 1984-07-07 1986-01-24 Foerfarande foer framstaellning av gamma-globulin vilket laempar sig foer intravenoest administration.
DK097286A DK164023C (da) 1984-07-07 1986-03-04 Fremgangsmaade til fremstilling af gammaglobulin, der er egnet til intravenoes indgivelse
NO86860848A NO168943C (no) 1984-07-07 1986-03-06 Fremgangsmaate ved fremstilling av gammaglobulin som er egnet for intravenoes administrering
JP7263622A JPH08319241A (ja) 1984-07-07 1995-09-19 静脈注射用ガンマグロブリン組成物

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP84107985A EP0168506B2 (fr) 1984-07-07 1984-07-07 Procédé de préparation de gamma-globuline pour l'injection intraveineuse
DE84107985.8(EP) 1984-07-07
JP7263622A JPH08319241A (ja) 1984-07-07 1995-09-19 静脈注射用ガンマグロブリン組成物

Publications (1)

Publication Number Publication Date
WO1986000530A1 true WO1986000530A1 (fr) 1986-01-30

Family

ID=26091956

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1985/000320 Ceased WO1986000530A1 (fr) 1984-07-07 1985-07-03 Procede de preparation de gamma globuline adequate pour une administration intraveineuse

Country Status (8)

Country Link
EP (1) EP0168506B2 (fr)
JP (2) JPH0816065B2 (fr)
AT (1) ATE59144T1 (fr)
DE (1) DE3483784D1 (fr)
DK (1) DK164023C (fr)
FI (1) FI84136C (fr)
NO (1) NO168943C (fr)
WO (1) WO1986000530A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8911741B2 (en) 2002-08-16 2014-12-16 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-alpha associated disorders

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0662436B2 (ja) * 1986-05-19 1994-08-17 株式会社ミドリ十字 静注用免疫グロブリン製剤の製造方法
DE4344824C1 (de) * 1993-12-28 1995-08-31 Immuno Ag Hochkonzentriertes Immunglobulin-Präparat und Verfahren zu seiner Herstellung
DE4424935C1 (de) * 1994-07-14 1996-03-21 Immuno Ag Humanes virussicheres monomeres Immunglobulin A und Verfahren zu seiner Herstellung
EP1380589A4 (fr) 2001-03-09 2004-09-01 Chugai Pharmaceutical Co Ltd Methode de purification de proteines
US9403899B2 (en) 2011-08-26 2016-08-02 Baxalta Incorporated Method for reducing the thromboembolic potential of a plasma-derived immunoglobulin composition

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2751717A1 (de) * 1976-12-03 1978-07-13 Myer Louis Dr Coval Neue verbesserte gammaglobuline fuer intravenoese injektion und verfahren zu ihrer herstellung
US4126605A (en) * 1975-12-29 1978-11-21 Plasmesco Ag Process of improving the compatibility of gamma globulins
EP0078331A1 (fr) * 1981-10-29 1983-05-11 Green Cross Corporation Procédé de préparation d'immunoglobuline pour l'injection intraveineuse

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2604759C2 (de) * 1976-02-07 1983-06-01 SCHURA Blutderivate GmbH & Co KG, 4150 Krefeld Verfahren zur Gewinnung von iv-verträglichen Γglobulinen
JPS6016406B2 (ja) * 1976-08-06 1985-04-25 マイヤ−、ル−イス、コ−バル 静脈内に投与可能なガンマ・グロブリンの製造法ならびにそれにより調製したガンマ・グロブリン
AT359641B (de) * 1978-09-19 1980-11-25 Immuno Ag Verfahren zur herstellung eines intravenoes ver- abreichbaren antikoerperhaeltigen immunglobulin- praeparates
JPS5732228A (en) * 1980-08-05 1982-02-20 Green Cross Corp:The Preparation of immunoglobulin usable for intravenous injection
JPS57203017A (en) * 1981-06-09 1982-12-13 Fujirebio Inc Purifying method of immunoglobulin

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4126605A (en) * 1975-12-29 1978-11-21 Plasmesco Ag Process of improving the compatibility of gamma globulins
DE2751717A1 (de) * 1976-12-03 1978-07-13 Myer Louis Dr Coval Neue verbesserte gammaglobuline fuer intravenoese injektion und verfahren zu ihrer herstellung
EP0078331A1 (fr) * 1981-10-29 1983-05-11 Green Cross Corporation Procédé de préparation d'immunoglobuline pour l'injection intraveineuse

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8911741B2 (en) 2002-08-16 2014-12-16 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-alpha associated disorders
US8916157B2 (en) 2002-08-16 2014-12-23 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-α associated disorders
US8916158B2 (en) 2002-08-16 2014-12-23 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-α associated disorders
US8932591B2 (en) 2002-08-16 2015-01-13 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-α associated disorders
US8940305B2 (en) 2002-08-16 2015-01-27 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-α associated disorders
US9114166B2 (en) 2002-08-16 2015-08-25 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-α associated disorders
US9220781B2 (en) 2002-08-16 2015-12-29 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9272042B2 (en) 2002-08-16 2016-03-01 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9272041B2 (en) 2002-08-16 2016-03-01 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9289497B2 (en) 2002-08-16 2016-03-22 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9295725B2 (en) 2002-08-16 2016-03-29 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9302011B2 (en) 2002-08-16 2016-04-05 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-α associated disorders
US9327032B2 (en) 2002-08-16 2016-05-03 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9732152B2 (en) 2002-08-16 2017-08-15 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9738714B2 (en) 2002-08-16 2017-08-22 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders
US9750808B2 (en) 2002-08-16 2017-09-05 Abbvie Biotechnology Ltd. Formulation of human antibodies for treating TNF-alpha associated disorders
US9950066B2 (en) 2002-08-16 2018-04-24 Abbvie Biotechnology Ltd Formulation of human antibodies for treating TNF-alpha associated disorders

Also Published As

Publication number Publication date
FI860350A0 (fi) 1986-01-24
DK97286A (da) 1986-03-04
JPS61500972A (ja) 1986-05-15
DE3483784D1 (de) 1991-01-31
FI84136C (fi) 1991-10-25
ATE59144T1 (de) 1991-01-15
FI84136B (fi) 1991-07-15
DK164023B (da) 1992-05-04
DK97286D0 (da) 1986-03-04
EP0168506B2 (fr) 1998-01-07
EP0168506B1 (fr) 1990-12-19
NO168943C (no) 1992-04-22
JPH0816065B2 (ja) 1996-02-21
NO860848L (no) 1986-03-06
JPH08319241A (ja) 1996-12-03
NO168943B (no) 1992-01-13
FI860350L (fi) 1986-01-24
DK164023C (da) 1992-09-28
EP0168506A1 (fr) 1986-01-22

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